Protection Against Infectious Bronchitis Virus Vaccine Recombinants and Chicken-Selected Vaccine Subpopulations.

Camila Cuadrado, Cassandra Breedlove, Edzard van Santen, Kelly S Joiner, Vicky L van Santen, Haroldo Toro
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Abstract

Outbreaks of infectious bronchitis (IB) continue to occur from novel variants of IB virus (IBV) emerging from selection of vaccine subpopulations and/or naturally occurring recombination events. S1 sequencing of Arkansas (Ark) -type viruses obtained from clinical cases in Alabama broilers and backyard chickens shows both Ark Delmarva Poultry Industry (ArkDPI) vaccine subpopulations as well as Ark vaccine viruses showing recombination with other IB vaccine viruses. IB Ark-type isolates AL5, most similar to an ArkDPI vaccine subpopulation selected in chickens, AL4, showing a cluster of three nonsynonymous changes from ArkDPI subpopulations selected in chickens, and AL9, showing recombination with Massachusetts (Mass) -type IBV, were examined for pathogenicity and ability to break through immunity elicited by vaccination with a commercial ArkDPI vaccine. Analysis of predicted S1 protein structures indicated the changes were in regions previously shown to comprise neutralizing epitopes. Thus, they were expected to contribute to immune escape and possibly virulence. Based on clinical signs, viral load, and histopathology, all three isolates caused disease in naïve chickens, although AL9 and AL5 viral loads in trachea were statistically significantly higher (30- and 40-fold) than AL4. S1 gene sequencing confirmed the stability of the relevant changes in the inoculated viruses in the chickens, although virus in some individual chickens exhibited additional S1 changes. A single amino acid deletion in the S1 NTD was identified in some individual chickens. The location of this deletion in the predicted structure of S1 suggested the possibility that it was a compensatory change for the reduced ability of AL4 to replicate in the trachea of naïve chickens. Chickens vaccinated with a commercial ArkDPI vaccine at day of hatch and challenged at 21 days of age showed that vaccination provided incomplete protection against challenge with these viruses. Moreover, based on viral RNA copy numbers in trachea, differences were detected in the ability of the vaccine to protect against these IBV isolates, with the vaccine protecting the most poorly against AL4. These results provide additional evidence supporting that IBV attenuated vaccines, especially ArkDPI vaccines, contribute to perpetuating the problem of IB in commercial chickens.

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对传染性支气管炎病毒重组疫苗和鸡选择疫苗亚群的保护。
由于疫苗亚群的选择和/或自然发生的重组事件而出现的新型 IB 病毒(IBV)变种,传染性支气管炎(IB)疫情持续爆发。从阿拉巴马州肉鸡和散养鸡的临床病例中获得的方舟(Ark)型病毒的 S1 测序显示,方舟-德尔马瓦家禽工业(ArkDPI)疫苗亚群以及方舟疫苗病毒与其他 IB 疫苗病毒发生了重组。对 IB 方舟型分离物 AL5(与在鸡中筛选出的 ArkDPI 疫苗亚群最为相似)、AL4(与在鸡中筛选出的 ArkDPI 亚群相比出现了三组非同义变化)和 AL9(与马萨诸塞州(Mass)型 IBV 病毒出现重组)进行了致病性和突破商用 ArkDPI 疫苗免疫力能力的检测。对预测的 S1 蛋白结构的分析表明,这些变化发生在以前被证明包含中和表位的区域。因此,预计这些变化将有助于免疫逃逸,并可能产生毒力。根据临床症状、病毒载量和组织病理学,所有三种分离株都会导致天真鸡发病,但 AL9 和 AL5 在气管中的病毒载量在统计学上明显高于 AL4(30 倍和 40 倍)。S1 基因测序证实了接种病毒在鸡体内相关变化的稳定性,尽管某些鸡体内的病毒表现出额外的 S1 变化。在一些鸡只中发现了 S1 NTD 的单个氨基酸缺失。这一缺失在 S1 预测结构中的位置表明,它可能是 AL4 在天真鸡气管中复制能力下降的一种补偿性变化。在孵化当天接种商业 ArkDPI 疫苗并在 21 日龄时接受挑战的鸡只表明,接种疫苗并不能完全保护鸡只免受这些病毒的挑战。此外,根据气管中的病毒 RNA 拷贝数,发现疫苗对这些 IBV 分离物的保护能力存在差异,其中疫苗对 AL4 的保护能力最弱。这些结果提供了更多证据,证明 IBV 减毒疫苗,尤其是 ArkDPI 疫苗会导致商品鸡 IB 问题长期存在。
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